Non-fouling, wettable coated devices

ABSTRACT

A device, and its production method, the device has a substrate and a coating composition, the coating composition being formed by the gas phase or plasma polymerization of a gas comprising at least one organic compound or monomer. The polymerization is carried out using a pulsed discharge having a duty cycle of less than about ⅕, in which the pulse-on time is less than about 100 msec and the pulse-off time is less than about 2000 msec. The duty cycle can also be varied, thus the coating composition can be gradient layered accordingly. The device has a coating composition which is uniform in thickness, pin-hole free, optically transparent in the visible region of the magnetic spectrum, permeable to oxygen, abrasive resistant, wettable and biologically non-fouling.

[0001] This is a continuation-in-part application of prior U.S. patentapplication Ser. No. 08/632,935, filed Apr. 16, 1996, the entire contentof which is hereby incorporated by reference.

[0002] The US Government has certain rights in the present inventionpursuant to the National Institutes of Health under Grant R01 AR43186-01and by the State of Texas through the Texas Higher EducationCoordinating Board ATP Program under Grant 003656-137.

[0003] This application claims the benefit of U.S. ProvisionalApplication Serial No. 60/055,260 filed on Aug. 8, 1997, and entitled“NON-FOULING WETTABLE COATED DEVICES,” commonly assigned with thepresent invention and incorporated herein by reference.

TECHNICAL FIELD

[0004] This invention relates to devices having gas-phase depositedcoatings and their methods of production. More specifically, thisinvention relates to devices, and their method of production, havinggas-phase deposited coatings which are non-fouling and wettable.

BACKGROUND

[0005] The chemical composition of surfaces plays a pivotal role indictating the overall efficacy of many devices. Some devices requirenon-fouling, and wettable surfaces in order for the devices to be usefulfor their intended purposes. For example, many biomedical devices suchas catheters, stents, implants, interocular lenses and contact lensesrequire surfaces which are biologically non-fouling, which means thatproteins, lipids, and cells will not adhere to the surfaces of thedevices. In some cases materials for devices are developed which haveall the necessary attributes for their intended purposes, such as,strength, optimal transmission, flexibility, stability, and gastransport except that the surfaces of the materials will foul when inuse. In these cases either new materials for the devices are developedor an attempt to change the surface characteristics of the materials ismade.

[0006] In the specific case of contact or interocular lenses,particularly contact lenses, although many polymeric materials possessthe necessary mechanical, oxygen permeation and optical propertiesrequired for lens manufacture, many potential contact lens materials aresubject to rapid biological fouling due to the adhesion of proteins,lipids, and other molecules present in the tear fluid surrounding thelens, and/or the surface energies of the materials are too low makingthe contact lenses too hydrophobic, and therefore not wettable by thetear fluid.

[0007] In light of the above considerations, a common approach utilizedby various researchers is to attempt to improve the biocompatibility ofthe potential contact lens materials by application of a thin coating tothese substrates. In theory such a coating would take advantage of theinherent favorable bulk mechanical, gas transport and optical propertiesof the polymer with the applied coating providing the requiredhydrophilicity and non-fouling properties. However, despite the plethoraof such studies, it is significant to note that, at present, not asingle contact lens manufacturer offers commercial products havingcoatings applied for this express purpose. Obviously, although theconcept of simply applying a surface coating to remedy physical propertydeficiencies of a given polymer substrate has theoretical appeal, thishas proven to be a totally illusive goal in actual practice. Theprevious failures reflect the fact that, to be commercially viable, asuccessful contact lens coating procedure must satisfy a myriad ofrather stringent requirements. These requirements, as a minimum, includethe following criteria: the coatings must be uniform and, ideally,pin-hole free; the coatings must be both wettable and non-biologicallyfouling; the coatings should be essentially devoid of extractables andthey must exhibit long-term chemical stability in aqueous salinesolution; the coatings must exhibit excellent optical transparency inthe visible region of the electromagnetic spectrum; the coatings mustnot compromise the oxygen permeability (i.e., the so-called DK value) ofthe polymer substrate; and, in the case of reusable lenses, the coatingsmust exhibit sufficient abrasion resistance and chemical stability towithstand repeated cleanings. In the latter case, cleaning procedureswould include both exposure to harsh chemical cleansing agents and tomechanical rubbing actions.

[0008] European Patent Application 93810399.1, filed Jun. 2, 1993,describes a complicated multi-step process to alter the surface of acontact lens material. The process requires a plasma treatment of thesurface to generate surface free radicals which are reacted with oxygento form hydroperoxy groups, to which are graft polymerized anethylenically unsaturated monomer plus cross-linking agent, followed bya solution extraction period to remove unreacted monomers. This complexprocess requires the presence of inhibition agents during the monomercoupling reactions to prevent the homopolymerization of the ethylenemonomers by free radicals generated during the thermal decomposition ofthe hydroperoxy groups.

[0009] The plasma deposition of triethylene glycol monoallyl ether isreported in the German patent application DE19548152.6. Although it didnot deal with contact lenses, it centered on surface modifications toreduce the adsorption of biological compounds. Coatings of such typewould be useful in reducing non-specific protein adsorption on certainbiosensor surfaces. In this work, substrates for coating were locatedoutside the plasma discharge zone and exceptionally low RF powerdensities were employed in an attempt to minimize fragmentation of thepolyethylene oxide units present in this monomer. Not unexpectedly,coatings deposited in the relatively non-energetic region upstream ofthe plasma discharge and outside the luminous discharge zone were onlyweakly attached to the underlying substrates. Another problemencountered in this work was the low volatility of the monomer. Thisresulted in a requirement for monomer heating to provide sufficientvapor for the plasma deposition process. However, even with heating, thevapor pressures obtainable without initiating thermal decomposition ofthe monomer were too low to provide any sort of flow rate and/or reactorpressure controllability. Additionally, the unusually low vapor pressureresulted in exceptionally low film deposition rates with accompanyingfilm non-uniformity. The coatings obtained were not tested for adhesionunder flow conditions, nor were they subjected to any abrasive cleaningor rubbing actions. Simple soaking of the coating substrates indistilled water for relatively short periods (e.g., less than 48 hours)resulted in measurable changes in the chemical compositions of thecoatings as revealed by XPS surface analysis of these coatings beforeand after the simple water immersion test.

[0010] U.S. Pat. Nos. 3,008,920 and 3,070,573 reveal the use of plasmasurface treatments to generate free radicals for subsequent peroxy groupformation followed by the grafting of vinylic monomers to the polymersubstrate. The control of the depth uniformity and density of thegrafted coatings is a difficult problem encountered in these graftingexperiments.

[0011] PCT/US90/05032 (Int. Publication #W091/04283) disclosesincreasing the wettability of polymeric contact lens materialssynthesized from specific hydroxy acrylic units and vinylic siloxanemonomers by grafting other molecules to the surface. The only examplesof the proposed grafting procedure described in this patent involveattachment of specific polyols by wet chemical procedures, but thispatent does suggest that hydroxy acrylic units may be grafted to thespecific hydroxy acrylic/siloxane polymeric materials by radiationmethods. Additionally, radiation induced attachment by gaseous hydroxylacrylic units was described in U.S. Pat. No. 4,143,949 as a means ofimproving surface hydrophilic character.

[0012] U.S. Pat. No. 4,143,949 discloses a process for putting ahydrophilic coating on a hydrophoic contact lens. The polymerization isachieved by subjecting a monomer, in gaseous state, to the influence ofelectromagnetic energy, of a frequency and power sufficient to cause anelectrodeless glow discharge of the monomer vapor.

[0013] U.S. Pat. No. 4,693,799 describes a process for producing aplasma polymerized film by pulse discharging. The process comprisesforming a plasma polymerized film on the surface of a substrate placedin a reaction zone by subjecting an organic compound containing gas toplasma polymerization utilizing low temperature plasma formed by pulsedischarging, in which the time of non-discharging condition is at least1 msec, and the voltage rise time for gas breakdown is not longer than100 msec. Specifically, the patent disclosed a process employing analternating current (“AC”) electrical discharge operated in a pulsedmode to provide films having small coefficients of friction and highlubricity for use on magnetic tapes and discs. Although variousexperimental sets were carried out at different AC frequencies (from 2to 2 Khz), all experiments within a given set were reportedly conductedat fixed plasma on to plasma off times. However, it provides no mentionof the film compositional control available via changes in the ratio ofplasma on to plasma off times during pulsed plasma polymerization of anorganic monomer; nor is any mention made of the adhesion of thedeposited films with respect to soaking or abrasive cleaning actions.

[0014] U.S. Pat. Nos. 3,854,982 and 3,916,033 describe the use of liquidcoating techniques to improve the wettability of contact lens polymers.In these procedures free radical polymerizable precursors, includinghydroxy alkyl methacrylates, are attached to contact lenses by exposureto high energy radiation. However, these solution attachment processesprovide poor control of the film thickness and these films exhibit poorabrasion resistance, particularly when attached to polysiliconesubstrates.

[0015] The direct plasma treatment to improve the wettability of contactlenses is described in U.S. Pat. No. 3,925,178 in which an electrical orradio frequency discharge in water vapor is employed for that purpose.This non-coating treatment results in a relatively unstable hydrophilicsurface in which the wettability of the contact lens substrate decreasesrapidly in time.

[0016] U.S. Pat. No. 5,153,072 describes a method of controlling thechemical structure of polymeric films by plasma deposition and filmsproduced thereby. The focus of this invention involves controlling thetemperature of the substrate and the reactor so as to create atemperature differential between the substrate and reactor such that theprecursor molecules are preferentially adsorbed or condensed on thesubstrate either during plasma deposition or between plasma depositionsteps.

[0017] Yasuda et al., “Some Aspects of Plasma PolymerizationInvestigated by Pulsed R. F. Discharge,” Journal of Polymer Science:Polymer Chemistry Edition, Vol. 15, pp. 81-97 (1977), discloses thepolymerization of organic compounds in glow discharge (plasmapolymerization) by using pulsed RF discharge (100 microsec. on, and 900microsec. off). The effect of pulsed discharge on polymer depositionrate, pressure change in plasma, ESR signals of free spins in bothplasma polymer and substrate, and the contact angle of water on theplasma polymer surface were investaged for various organic compounds.

[0018] Nakajima et al., “Plasma Polymerization of Tetrafluoroethylene,”Journal of Applied Polymer Science, Vol. 23, pp. 2627-2637 (1979),describes the plasma polymerization of tetrafluoroethylene in bothcontinuous wave and pulsed radio frequency (“RF”) discharges. Theyreported that both polymer deposition rates and polymer structures wereessentially identical when using continuous wave and pulsed RFdischarge.

[0019] Lopez et al., “Glow discharge plasma deposition of tertraethyleneglycol dimethyl ether for fouling-resistant biomaterial surfaces,”Journal of Biomedical Materials Research, Vol. 26, pp 415-439 (1992),discloses the glow discharge plasma deposition of tetraethylene glycoldimethyl ether onto glass, polytetrafluoroethylene and polyethylene. Themonomer required heating, and low power to retain the ethylene oxidecontent of the plasma deposited coatings. As a result, no monomer flowrate controllability was available, and the films deposited at the lowerRF powers exhibited low stability to even simple overnight soaking inwater. The film adhesion to the polymeric substrate could be improved bycarrying cut the plasma deposition at higher power but this improvedadhesion was achieved at the expense of loss of ethylene oxide fimcontent and thus poorer non-fouling properties.

[0020] The need still remains for a composition which can be applied tothe surface of a substrate to provide a fin of coating that is uniformin thickness, pin-hole free, optically transparent in the visible regionof the magnetic spectrum, permeable to oxygen, biologically non-fouling,relatively abrasive resistant, and wettable (hydrophilic).

SUMMARY

[0021] The present invention provides a device comprising a substrateand a coating composition, the coating composition being formed by thegas phase or plasma polymerization of a gas comprising at least oneorganic compound or monomer, the organic compound having the followingstructure:

[0022] m 0-1; n=0-6,

[0023] where Y represents C=0;

[0024] R¹, R², R³, R⁴, R⁵, R⁶ and R⁷ each independently represents:

[0025] H,

[0026] OH,

[0027] halogen,

[0028] C₁-C₄ alkyl,

[0029] C₁-C₄ alkene,

[0030] C₁-C₄ diene,

[0031] C₁-C₄ alkyne,

[0032] C₁-C₄ alkoxy, or

[0033] C₁-C₄ alkyl halide; and

[0034] R⁸ represents:

[0035] H,

[0036] halogen,

[0037] C₁-C₄ alkyl,

[0038] C₁-C₄ alkene,

[0039] C₁-C₄ diene,

[0040] C₁-C₄ alkyne,

[0041] C₁-C₄ alkyl halide,

[0042] C₁-C₄ aldehyde,

[0043] C₁-C₄ ketone,

[0044] C₁-C₄ epoxide,

[0045] C₁-C₄ carboxylic acid,

[0046] C₁-C₄ ester,

[0047] —CH═CHR⁹, where R⁹ is H, halogen, C₁-C₄ alkyl, C₁-C₄ alkylhalide, C₁-C₄ aldehyde, C₁-C₄ ketone, C₁-C₄ alkoxyl, C₁-C₄ epoxide,C₁-C₄ carboxylic acid, or C₁-C₄ ester, or

[0048] —OR¹⁰, where R¹⁰ is H, halogen, C₁-C₄ alkyl, C₁-C₄ alkene, C₁-C₄diene, C₁-C₄ alkyne, C₁-C₄ alkyl halide, C₁-C₄ aldehyde, C₁-C₄ ketone,C₁-C₄ epoxide, C₁-C₄ carboxylic acid, or C₁-C₄ ester.

[0049] The polymerization of the present invention can be carried outusing a pulsed discharge having a duty cycle of less than about ⅕, inwhich the pulse-off time is less than about 2000 msec and the pulse-ontime is less than about 100 msec. The duty cycle can also be varied,thus the coating composition can be gradient layered accordingly.

[0050] The compound generally has low molecular weight, one or moreether linkages and at least one unsaturated carbon-carbon bond.

[0051] The devices of this invention have coating compositions which areuniform in thickness, pin-hole free, optically transparent in thevisible region of the magnetic spectrum, permeable to oxygen, abrasiveresistant, wettable and biologically non-fouling; therefore, making itpossible to use substrates which, except for their surfacecharacteristics, are well suited for their intended uses. In thespecific case of contact or interocular lenses, particularly contactlenses, substrates which are not wettable by the tear fluid, which aresubject to rapid biological fouling, and/or have surface energies whichare too low can be made useful, when coated with the coatingcompositions of this invention.

[0052] The coatings of the present invention are deposited on thesurface of a solid substrate via plasma polymerization of at least oneselected monomer. The plasma deposition of the present invention isachieved by either continuous wave (“CW”) or pulsed plasmas. In thepulsed mode, the deposition is carried out of a fixed plasma duty cycleor, alternately, using a variable duty cycle pulsed plasma deposition.

BRIEF DESCRIPTION OF THE DRAWINGS

[0053]FIG. 1 is an illustration of the variation in coating wettabilitywith changes in RF duty cycles employed during deposition, while allother plasma reaction variables were being held constant.

[0054] FIGS. 2(a-d) are illustrations of the variation in coatingcomposition with changes in RF duty cycles employed during deposition ofplasma polymerized EO2V film at 200 watts, while all other plasmareaction variables were being held constant. The numerator given belowdenotes the plasma-on time, and the denominator given below denotes theplasma-off time, both in the unit of msec. High resolution C (Is) XPSspectra are shown for films deposited at RF on/off ratio (in msec) of:(a) 1/20; (b) 1/50; (c) 1/100; and (d) 1/200.

[0055]FIG. 3 is an illustration of the variation in coating wettabilitywith changes in RF peak power employed during deposition, at a constantplasma on/off ratio of 10/200 msec, all other plasma reaction variableswere held constant.

[0056] FIGS. 4(a-b) are illustrations of the stability of EO2V plasmafilms to prolonged exposure to air. The EO2V plasma film was depositedat a plasma-on time of 10 msec and a plasma-off time of 200 msec at 50watts. The spectra shown are C (1s) XPS results of these films: (a)after exposure to air for 10 months; and (b) fresh film.

[0057] FIGS. 5(a-e) are illustrations of XPS high resolution C (is)spectra of plasma polymerized EO2V films obtained from a series of runscarried out at a fixed plasma-on to plasma-off ratio of 1 to 20 at 50Wbut with varying actual plasma-on and plasma-off pulse width: (a) 100msec on and 2000 msec off; (b) 10 msec on and 200 msec off; (c) 1 msecon and 20 msec off; (d) 0.1 msec on and 2 msec off; and (e) 0.01 msec onand 0.2 msec off.

DETAILED DESCRIPTION

[0058] The devices of this invention comprise non-fouling coatingcompositions. The coating compositions provide surfaces which areuniform, pin-hole free, wettable, devoid of extractables, and chemicallystable. Further, the coatings exhibit excellent optical transparency inthe visible region of the electromagnetic spectrum, are oxygenpermeable, and are abrasion resistant. These are desirablecharacteristics particularly for biomedical devices, such as stents,implants, catheters, etc., and particularly for contact or interoccularlenses. The coating of the present invention is also suitable forsurface coating of magnetic recording media, magnetic tapes, magneticdiscs, cell cultivation bed, carriers for diagnostic reagents,biosensors, and artificial organs, such as artificial blood vessels,artificial bones, and others.

[0059] The substrates for the devices of this invention can comprisepolymers, plastic, ceramics, glass, silanized glass, fabrics, paper,metals, silanized metals, silicon, carbon, silicones and hydogels. Someof the more preferred materials include those that are likely to be usedfor biomedical devices, such as silicone and silicone containingcompositions, (mixed blends and copolymers), polyurethanes, andhydrogels, and mixtures of these materials. The most preferred substratematerials are those polymers used to make contact lenses, which do notsupport a stable tear film on the surface, such as silicones, siliconemixed blends, alkoxylated methyl glucosides, silicone hydrogels,polyurethane-silicone hydrogels, and polysulfones. Illustrativesilicones are polydimethylsiloxane polydimethyl-co-vinylmethylsiloxane,silicone rubbers described in U.S. Pat. No. 3,228,741, silicone blendssuch as those described in U.S. Pat. No. 3,341,490, and siliconecompositions such as described in U.S. Pat. No. 3,518,324. Usefulsilicone materials are the cross linked polysiloxanes obtained by crosslinking siloxane prepolymers by means of hydrosilylation, cocondensationand by free radical mechanisms. Particularly suitable substratematerials are organopolysilioxane polymer mixtures which readily undergohydrosilylation. Such prepolymers will comprise vinyl radicals andhydride radicals which serve as crosslinking sites during chainextension and crosslinking reaction and are of the general formulationcomprising polydihydrocarbyl-co-vinylhydrocarbyl siloxane andpolydihydrocarbyl-co-hydrocarbylhydrogensiloxanes wherein thehydrocarbyl radicals are monovalent hydrocarbon radicals such as alkylradicals having 1-7 carbon atoms, such as, methyl, ethyl, propyl, butyl,pentyl, hexyl and heptyl; aryl radicals, such as phenyl, tolyl, xylyl,biphenyl; haloaryl, such as chlorophenyl and cycloalkyl radicals such ascyclopentyl, cyclohexyl, etc. The more preferred materials are siliconehydrogels, particularly silicone-hydrogels formed from monomer mixturescomprising an acrylic-capped polysiloxane prepolymer, a bulkypolysiloxanylalkyl (meth)acrylate monomer and hydrophilic monomers asdescribed in U.S. Pat. Nos. 5,387,632; 5,358,995; 4,954,586; 5,023,305;5,034,461; 4,343,927; and 4,780,515. Other preferred substrate materialscomprise cyclic polyols of alkoxylated glucose or sucrose like thosedescribed in U.S. Pat. No. 5,196,458 and 5,304,584, and U.S. patentapplication Ser. No. 08/712,657, filed Sep. 13, 1996. All of the patentscited above are incorporated herein by reference.

[0060] The preferred coating compositions comprise gas phase depositedlow molecular weight, high volatility organic compounds containing oneor more ether linkages. Preferably, the molecules contain at least oneunsaturated carbon-carbon bond in the molecule to assist in achievingpolymerization, particularly under low energy gas-phase depositionmethods. The groups having unsaturated carbon-carbon bonds arepreferably vinyl compounds. The coating compositions are stable, andadherent to a wide range of substrates while maintaining maximumintegrity of the ether linkages present in these monomers. The weightaverage molecular weights of the compounds are preferably less than 400,more preferably less than 300, and most preferably less than 200.

[0061] The preferred coating compositions are formed by the gas phasedeposition and polymerization of a linear or branched organic compoundor monomer having the following structure:

[0062] m 0-1; n=0-6,

[0063] where Y represents C=0;

[0064] R¹, R², R³, R⁴, R⁵, R⁶ and R⁷ each independently represents:

[0065] H,

[0066] OH,

[0067] halogen,

[0068] C₁-C₄ alkyl,

[0069] C₁-C₄ alkene,

[0070] C₁-C₄ diene,

[0071] C₁-C₄ alkyne,

[0072] C₁-C₄ alkoxy, or

[0073] C₁-C₄ alkyl halide; and

[0074] R⁸ represents:

[0075] H,

[0076] halogen,

[0077] C₁-C₄ alkyl,

[0078] C₁-C₄ alkene,

[0079] C₁-C₄ diene,

[0080] C₁-C₄ alkyne,

[0081] C₁-C₄ alkyl halide,

[0082] C₁-C₄ aldehyde,

[0083] C₁-C₄ ketone,

[0084] C₁-C₄ epoxide,

[0085] C₁-C₄ carboxylic acid,

[0086] C₁-C₄ ester,

[0087] —CH═CHR⁹, where R⁹ is H, halogen, C₁-C₄ alkyl, C₁-C₄ alkylhalide, C₁-C₄ aldehyde, C₁-C₄ ketone, C₁-C₄ alkoxyl C₁-C₄ epoxide, C₁-C₄carboxylic acid, or C₁-C₄ ester, or

[0088] —OR¹⁰, where R¹⁰ is H, halogen, C₁-C₄ alkyl, C₁-C₄ alkene, C₁-C₄diene, C₁-C₄ alkyne, C₁-C₄ alkyl halide, C₁-C₄ aldehyde, C₁-C₄ ketone,C₁-C₄ epoxide, C₁-C₄ carboxylic acid, or C₁-C₄ ester.

[0089] Examples of usable organic compounds include the followingstructures:

R′C(R″)═C(R′″)—(OCH₂CH₂)_(n)—OR″″

R′C(R″)═C(R′″)—(OCH₂CH₂)_(n)—R″″

R′C(R″)═C(R′″)—C(O)—(OCH₂CH₂)_(n)—OR″″

[0090] and R′C(R″)═C(R′″)—C(O)—(OCH₂CH₂)_(n)—R″″

[0091] where R′, R″, R′″, and R″″ independently represent H, a linear orbranched alkyl having 1 to 4 carbons; preferably methyl or H; morepreferably H; and n is 1 to 6; preferably 1 to 5; more preferably 2 or3. For specifically preferred monomers having the above structuralformulas R′, R″, R′″, and R″″ are H; or R′, R″, R′″ are H, and R″″ isCH₃; and n is 2 or 3, more preferably 2.

[0092] Example of more specific usable organic compounds include:

CH₂═CH—(OCH₂CH₂)_(n)—OH

CH₂═CH—(OCH₂CH₂)_(b)—OCH₃

CH₂═CH—(OCH₂CH₂)—OCH═CH₂

[0093] Other examples of usable organic compounds in the coatingcomposition of this invention include:

[0094] di(ethylene glycol) divinyl ether (H₂C═CHOCH₂CH₂)₂O

[0095] di(ethylene glycol) vinyl ether H₂C═CH(OCH₂CH₂)₂OH

[0096] di(ethylene glycol) methyl vinyl ether H₂C═CH(OCH₂CH)20CH₃

[0097] di(ethylene glycol) diacrylate (H₂C═CHCO₂CH₂CH₂)₂O

[0098] di(ethylene glycol) ethyl ether acrylateH₂C═CHC(O)(OCH₂CH₂)₂OC₂H₅

[0099] trimethylolpropane diallyl ether C₂H₅C(CH₂OCH₂CH═CH₂)₂CH₂OH

[0100] tetra(ethylene glycol) propyl ether methacrylateH₂C═C(CH₃)CO₂(OCH₂CH₂)₄CH₂CH₂CH₃

[0101] hexa(ethylene glycol) methyl ether methacrylateH₂C═C(CH₃)CO₂(OCH₂CH₂)₆CH₃

[0102] The more preferred organic compounds include di(ethylene glycol)divinyl ether, di(ethylene glycol) methyl vinyl ether, di(ethyleneglycol) ethyl ether acrylate, and trimethylolpropane diallyl ether. Themost preferred compound is di(ethylene glycol) vinyl ether.

[0103] The coating compositions can comprise the polymerization ofsubstantially a single organic compound or of a mixture of organiccompounds with or without the addition of cross-linking agents. Thesingle and the mixture of organic compounds preferably are selected fromthe organic compounds described above.

[0104] The selection of compounds and method of application of thecompounds to the surface of the substrate preferably provide a coatingcomposition in which the outermost layer of the coating has a ratio ofcarbon-oxygen bonds to carbon-carbon bonds of greater than 1:1, morepreferably greater than 1.5:1, and most preferably greater than 2:1,even more preferred is greater than 2.5:1. The coating compositionshaving a higher ratio of carbon-oxygen bonds to carbon-carbon bonds arepreferred, because of improved non-fouling and higher wettabilitycharacteristics.

[0105] One method for depositing the coating compositions on thesubstrates is by gas phase deposition, because it provides uniformcoating compositions. Gas phase deposition means by any method thegaseous monomers are attached to the solid substrate as a surfacecoating. Gas phase depositions include plasma and photochemical inducedpolymerizations. Plasma induced polymerizations or plasma depositionsare polymerizations due to the generations of free radicals caused bypassing an electrical discharge through a gas. The electrical dischargecan be caused by high voltage methods, either alternating current (“AC”)or direct current (“DC”), or by electromagnetic methods, such as, radiofrequency (“RF”) and microwave. Alternatively, the coating process canbe carried out using photochemical induced polymerizations as providedby direct absorption of photons of sufficient energy to create freeradicals and/or electronically excited species capable of initiation ofthe polymerization process.

[0106] One preferred method of one-step gas phase deposition is byplasma polymerization, particularly radio frequency plasmapolymerization, in which the coating is deposited on the surface of thesubstrate via direct monomer polymerization. This process will bedescribed herein. It is more fully described in U.S. patent applicationSer. No. 08/632,935, incorporated herein by reference. Additionaldescriptions can be found in Panchalingam et al., “Molecular SurfaceTailoring of Biomaterials Via Pulsed RF Plasma Discharges,” J. Biomater.Sci. Polymer Edn., Vol. 5, pp. 131-145 (1993), and Panchalingam et al,“Molecular Tailoring of Surfaces Via Pulsed RF Plasma Depositions,”Journal of Applied Science: Applied Polymer Symposium, 54, 123-141(1994), incorporated herein by reference. In this method, coatings aredeposited on solid substrates via plasma polymerization of selectedmonomers under controlled conditions. The plasma is driven by RFradiation using coaxial external RF electrodes located around theexterior of a cylindrical reactor. Substrates to be coated arepreferably located in the reactor between the RF electrodes; however,substrates can be located either before or after the electrodes. Thereactor is evacuated to background pressure using a rotary vacuum pump.A fine metering valve is opened to permit vapor of the monomer (ormonomer mixtures) to enter the reactor. The pressure and flow rate ofthe monomer through the reactor is controlled by adjustments of themetering valve and a butterfly control valve (connected to a pressurecontroller) located downstream of the reactor. In general, the monomerreactor pressures employed range from approximately 50 to 200 mili-torr,although values outside this range can also be utilized. It is preferredthat the compounds have sufficiently high vapor pressures so that thecompounds do not have to be heated above room temperature (from about 20to about 25° C.) to vaporize the compounds. Although the electrodes arelocated exterior to the reactor, the process of the invention worksequally well for electrodes located inside the reactor (i.e. acapacitively coupled system).

[0107] The chemical composition of a film obtained during plasmadeposition is a strong function of the plasma variables employed,particularly the RF power used to initiate the polymerization processes.It is preferred to operate the plasma process under pulsed conditions,compared to continuous wave (“CW”) operation, because it is possible toemploy reasonably large peak powers during the plasma on initiation stepwhile maintaining a low average power over the course of the coatingprocess. Pulsing means that the power to produce the plasma is turned onand off. The average power under pulsing is defined as:${{Average}\quad {Power}} = {\frac{{plasma}\text{-}{on}\quad {time}}{{{plasma}\text{-}{on}\quad {time}} + {{plasma}\text{-}{off}\quad {time}}} \times {Peak}\quad {Power}}$

[0108] For example, a plasma deposition carried out at a RF duty cycleof 10 msec on and 200 msec off and a peak power of 25 watts correspondsto an average power of 1.2 watts. The Peak Power is preferably betweenabout 10 and about 300 watts.

[0109] The formal definition of duty cycle is defined as the ratio ofthe plasma on time (i.e. discharge time) to a sum of the plasma-on timeand the plasma-off time (i.e. non-discharge time), as represented below:${{Duty}\quad {cycle}} = \frac{{plasma}\text{-}{on}\quad {time}}{{{plasma}\text{-}{on}\quad {time}} + {{plasma}\text{-}{off}\quad {time}}}$

[0110] However, for convenience, the plasma on to plasma off times arefrequently cited herein as a simple ratio of on to off time, both timesemploying the same scale (i.e. milliseconds or microseconds).

[0111] The workable range of duty cycle is less than about 1/5, thepreferred range is between about 1/10 and about 1/1000, and the morepreferred range is between about 1/10 and about 1/30. The plasma-on timeshould be larger than about 1 μsec, preferably in the range of betweenabout 10 μsec and about 100 msec, and more preferably in the range ofbetween about 100 μsec and about 10 msec. The plasma off time, i.e. thenon-discharge time, should be larger than about 4 μsec, preferably inthe range of between about 100 μsec and 2000 msec, and more preferablyin the range of between about 200 μsec and about 100 msec. The totaldeposition time varies depending on the monomer and the conditions used.Typically, the deposition time can vary from about 0.5 min to about 3hours.

[0112] Pulsed plasma deposition permits use of relatively high peakpowers while simultaneously maintaining relatively low average powerswhich provides for the retention of monomer functional groups. Coatingcompositions deposited under low average power pulsed conditions tend tobe more adhesive to a given substrate when compared to films depositedat the same average power but under CW operation. For a given averagepower, the momentary high peak power available under pulsed conditionsapparently assists in obtaining a stronger grafting of the film to thesubstrate than that obtained under the same average power CW conditions.

[0113] For a given RF peak power, an increased retention of the ethercontent (C—O functionality) of the plasma generated coating is observedas the plasma duty cycle is reduced when working with a given monomer.Alternatively, the chemistry of the coating composition can be variedunder pulsed conditions by working at a single plasma duty cycle butvarying peak powers. There is an increased incorporation of C—Ofunctionality in coating compositions as the peak power is decreased.Surprisingly, the plasma generated film composition can be varied bychanging the plasma on to plasma off pulse widths, at a fixed ratio ofplasma on to plasma off times and at a fixed RF peak power. Although thefilm deposition mode described is one of RF plasma polymerization, thosefamiliar in the art will recognize that other polymerization methods(e.g., microwave plasmas, photo-polymerization, ionizing radiation,electrical discharges, etc.) could also be adapted for this purpose.

[0114] The chemical composition of the films of this invention can bevaried during pulsed plasma deposition, by varying the peak power and/orthe duration of the plasma on and plasma off pulse widths. Thisexcellent film chemistry controllability is achieved without recourse tomodulating the temperature of the substrate during the actual coatingprocess. To produce a coating composition with the preferred ratio ofC—O functionality to C—C functionality, it is preferred that the averagepower of the pulsed plasma deposition is less than 100 watts, morepreferably less than 40 watts, most preferably less than 10 watts. Thehighest ratios of C—O functionality to C—C functionality can be obtainedwhen the average power is 1 watt and less which provides the mostnon-fouling and wettable coating compositions.

[0115] However, as those skilled in the art will recognize, the actualeffect of peak power input on film composition is dependent on thereactor volume (i.e. power density). In the present invention, thereactor volume is approximately 2 liters. Obviously, if a smallerreactor were employed, the same film compositioned changes reportedherein would be achieved at lower peak power inputs. Other reactionvariables which would influence peak power inputs are reactor pressureand monomer(s) flow rates. If larger reactor volumes were employed, thesame film compositional variations could be achieved using higher powerinput.

[0116] The use of lower average power conditions increases the presenceof functional groups, e.g. ether units, in the coatings, but the lessenergetic deposition conditions at lower average power may result inpoorer adhesion of the polymer film to the underlying substrate Thus,the plasma coating process involves somewhat of a compromise betweenretention of monomer integrity in the plasma generated film and thestrength of the adhesion between the coating and the solid substrate. Inthe case of biomedical devices and contact lenses, the adhesion andoverall stability of the coating composition to the lens substrate is anextremely important consideration.

[0117] One method of applying the coating compositions to the substrateof the present invention is by pulsed plasma coupled with gradientlayering. The duty cycle can be varied, thus creating variable dutycycle. The method can be used to maximize the adhesion of the coatingcomposition and the functionalities present in the coating composition.Films deposited under low average power pulsed conditions tend to bemore adhesive to a given substrate when compared to films deposited atthe same average power but under CW operation. For a given averagepower, the momentary high peak power available under pulsed conditionsassists in obtaining a stronger grafting of the film to the substratethan that obtained under the same average power CW condition. Thisstronger grafting under pulsed conditions is repeated with each plasmaon cycle. The better grafting of the film to the substrate obtainedunder pulsed conditions can be even further enhanced by combining thepulsed deposition with a gradient layering technique. This method isdescribed further in U.S. patent application Ser. No. 08/632,935, whichis incorporated herein by reference. In this process, an initial highpower, high plasma duty cycle is employed to graft the plasma generatedcoating composition tightly to the underlying substrate. The plasma dutycycle is subsequently progressively decreased in a systematic manner,with each decrease resulting in an increased retention of the C—Ofunctionality in the coating. In this way, the successive plasmadeposited films are tightly bonded to each other. The process isterminated when the exterior film layer has reached the desiredcomposition. The succession of thin layers, each differing slightly incomposition in a progressive fashion from the preceding one, results ina significantly more adhesive composite coating composition bonded tothe substrate than coatings deposited without adjusting the depositionconditions under a relatively lower plasma duty cycle.

[0118] Gas-phase deposition, particularly plasma depositions, providecoating compositions of substantially uniform thickness. The thicknessesof the coating composition could be between 5 Å and 5 μm, morepreferably between 50 Å and 1 μm, and most preferably between 100 Å and0.1 μm. The uniform film thickness and controllability of the depositionmethod can be contrasted, with thickness controllability problemsencountered using previously disclosed methods. Using the RF pulsedplasma deposition provides linearity of the thickness of the coatingcomposition with deposition time for a given plasma duty cycle and fixedmonomer pressure and flow rate.

[0119] The coatings of this invention increase the hydrophilic characterof the surface of the substrates, particularly with substrates that aremore hydrophobic (e.g., polysiloxanes). The extent of hydrophilicityintroduced during the plasma process was observed to increase as theoxygen content of the plasma generated coating compositions increased.

[0120] The wettabilities of the substrates employed were measured beforeand after plasma coating using both static and dynamic water contactangle measurements. In general, the coatings applied serves to increasethe hydrophilic character of the surface, particularly with substratesthat are more hydrophobic (e.g., polysiloxanes). The extent ofhydrophilicity introduced during the plasma process was observed toincrease as the oxygen content of the plasma generated films increased.

[0121] The stability of the surface wettability was examined in severalways, including exposure to aqueous solution flow and to abrasivecleaning and rubbing tests. Additional successful stability testing ofthe coated substrates involved autoclaving for five cycles at 121° C.for 30 minutes each cycle. The examples below include the results ofthese tests.

[0122] The non-fouling character of the coating compositions weremeasured using adsorption studies with radioactively labeled proteins,as well as by total protein assay. In general, decreases in proteinadsorption were observed for coated polymer substrates as compared touncoated polymer substrate as shown in the examples which follow.

[0123] The optical transparency of the coating compositions was measuredspectrophotometrically at wavelengths ranging from 800 to 200 nm. Theplasma coating compositions of the invention exhibited consistentexcellent transparency over the entire region of the visible spectrum(i.e., from 780 to 380 nm) with photon absorption beginning to occuraround 370 nm in the near w region. The absorption increases sharplyover the interval from 370 to 200 nm, as revealed by samples depositedon quartz plates.

[0124] The oxygen permeability was measured using the Fatt Method (Fatt,I. et al, International Contact Lens Clinic, 9(2), pp. 76-88 1992). Ingeneral, the oxygen permeabilities (reported as DK values) of thepolymeric substrates were not measurably decreased by the presence ofthe plasma film on the surface.

[0125] The substrates with coating compositions of this invention aresuited for contact lenses and other biomedical devices. The coatingcompositions exhibit good adhesion, high wettability, high oxygenpermeability, and excellent transparency in the visible region of theelectromagnetic spectrum when deposited on polymer substrates. Theadhesion of the coating compositions to these substrates aresufficiently strong to resist delamination.

[0126] Thus the coating composition applied by a one-step and all-dryprocess of this invention satisfies the stringent criteria listed aboveto improve the biocompatibility of contact lenses. The emphasis in thisinvention has been placed on the contact lenses; however, those skilledin the art will recognize that the highly wettable, biologicallynon-fouling, transparent coatings of this invention are useful forvarious other applications (e.g., biomedical devices, biosensors,detectors deployed in marine environments, membranes, tissue culturegrowth, implants, etc.). A particularly surprising result obtained inthe present study is the remarkably stable and good biologicallynon-fouling properties of these coatings despite the very low molecularweights of the monomers employed to form the coating compositions. Thisobservation is contrary to many previous studies which conclude thatrelatively large polymeric molecules containing ether linkages arerequired in order to observe the non-fouling effect.

[0127] The approach of the present invention represents an unusuallysimple, one-step coating process which could be conveniently coupledwith a plasma based sterilization procedure to provide large scalefabrication polyethyleneglycol (“PEG”) modified surfaces. Additionalinherent advantages of a plasma based approach would include successfulsurface modifications being less dependent on the composition andgeometry of the solid substrates. Tetraethylene glycol dimethyl ether,CH₃O(CH₂CH₂O)₄CH₃, and tri(ethylene glycol) monoallyl ether,CH₂═CHCH₂(OCH₂CH₂)₃OH, were studied as potential monomers for plasmapolymerized PEG surfaces. For example, tetraethylene glycol dimethylether was plasma deposited to yield surfaces with high short-termresistance to biomolecular absorption, as demonstrated with both plasmaprotein and cellular adsorption studies. However, simple overnightsoaking of plasma coated substrates in water resulted in major chemicalcompositional changes as revealed by XPS analysis of surfaces before andafter soaking. Similarly, plasma polymerization of tri(ethylene glycol)monoallyl ether produced coatings having good short term resistance tobiofouling but poor stability towards soaking or exposure to flowingaqueous solutions. Adhesion of the plasma films to the polymericsubstrates could theoretically be improved by carrying out the plasmadeposition at higher power but this improved adhesion was achieved atthe expense of loss of ethylene oxide film content and thus poorernon-fouling properties.

[0128] Although not wishing to be bound by any particular postulate, itis speculated that the gas phase deposition process, particularly thepulsed plasma deposition process of the present invention results in anunusually efficient stacking of ether linkages on the substrate surfacethus providing a high surface density of such groups. This high surfacedensity is, in turn, extremely effective in preventing the adsorption ofbiological molecules onto the surface while simultaneously creating arelatively polar environment to adsorb water molecules, thus providinghigh surface wettability. When the coating process is used for contactlenses, the coating composition on the contact lens substrate shouldprovide a low water contact angle. For contact lenses, it is preferredthat the coating compositions have an advancing sessile drop watercontact angle of less than 85°, more preferably less than 65°, mostpreferably less than 45°.

Example 1

[0129] Di(ethylene glycol) vinyl ether (EO2V) was plasma deposited on aDacron™ polyester substrate under pulsed plasma deposition conditionsusing an RF on/off cycle of 10 msec on and 200 msec off at 100 W peakpower. A 1000 Å thick film was deposited during the 20 minute run. X-rayphotoelectron spectroscopy (XPS) analysis of this film revealedsignificantly more carbon atoms bonded to oxygen than to other carbonatoms. A sample prepared in this manner was then subjected to 65 hoursof a constant 40 ml/min flow of phosphate buffer solution (PBS) at pH of7.4. The sample was subsequently vacuum dried and re-analyzed by XPS.The relative concentration of C—O to C—C groups present on the surfacehad actually increased slightly revealing negligible surfacemodification during the buffer flow, indicating the durability of thecoating composition.

Example 2

[0130] A sample prepared as described in Example I was deposited on asilicone contact lens substrate. The advancing water contact angle wasmeasured on the polysiloxane before and after plasma treatment. Theadvancing sessile drop water contact angle of 98° observed on theuntreated surface had decreased to 58° after surface coating by theplasma, indicating an increased wettability due to the coatingcomposition. Subsequent soaking of the coated sample in PBS buffersolution for several days resulted in essentially negligible change inthe advancing water contact angles, indicating the durability of thecoating composition. See, TABLE I. The ratio 10/200 in TABLE I indicates10 msec plasma-on time and 200 msec plasma-off time. TABLE I ContactAngle Variation for EO2V Films on Silicone Contact Lenses as a Functionof Soaking Time in PBS Buffer Solution Coating Fresh Condition Film 5hrs 10 hrs 48 hrs 96 hrs 240 hrs 10/200, 100w, 58 60 66 63 60 60 15 min10/200, 100w, 58 62 58 62 60 60 30 min

EXAMPLE 3

[0131] Samples were prepared as described in Example 1 on a polyethylenesubstrate, but at various plasma on/off cycles of on-time inmsec/off-time in msec of 1/20, 1/50, 1/100, and 1/200 at a peak power of200 watts. Analysis of these films by water contact angle goniometryrevealed progressively lower advancing water contact anglescorresponding to lower RF plasma duty cycles employed during the coatingprocedure. (FIG. 1) The increased wettability observed with decreasingaverage power during film formation is correlated with high resolution C(1s) XPS spectra of these films which show increasing C—O versus C—Cfilm content with decreasing RF duty cycle employed during filmformation. (FIGS. 2(a-d)).

[0132] Another set of samples were prepared as described in Example 1 ona Dacron™ substrate but at various plasma peak power of 100 watts, 50watts, 25 watts and 10 watts and at a cycle of 10 msec on and 200 msecoff. Analysis of these films by water contact angle goniometry revealedprogressively lower advancing water contact angles corresponding tolower RF plasma peak power employed during the coating procedure. (FIG.3). The increased wettability observed with decreasing average plasmaenergy correlated with XPS analysis of these films which showedincreasing C—O versus C—C film content with decreasing RF peak poweremployed during film formation.

EXAMPLE 4

[0133] The monomer CH₂—CH—(OCH₂CH₂)₂OCH₃ (Methyl EO2V) was plasmadeposited on a polysiloxane substrate using the same RF duty cycle andpeak power employed in Example 1. The resulting film revealed slightlyhigher C—O content relative to C—C bonds than obtained in Example 1.Additionally, these films exhibited an advancing water contact anglewhich was approximately 5° less (i.e., more hydrophilic) than thatobtained in Example 2.

EXAMPLE 5

[0134] A coating was prepared from the monomer di(ethylene glycol)divinyl ether [(H₂C═CHOCH₂CH₂)₂O] using the same plasma depositionconditions employed in Examples 1 and 4. The advancing water contactangle for this sample was virtually identical to that obtained for themethoxy compound of Example 4. Both the methoxy and divinyl samples ofExamples 4 and 5 revealed less hysteresis in terms of advancing versusreceding water contact angles than observed for the sample of Example 2,indicating that the surface molecules are less mobile, and thereforeless likely to foul. Further, the contact angles indicate that thesurfaces are wettable.

EXAMPLE 6

[0135] A sample was prepared in which the monomer of Example 1 wasplasma deposited onto a Dacron™ sample using an RF on/off cycle of 10msec on and 200 msec off and a peak power of 50 watts. Proteinadsorption using ²⁵I-labeled albumin and fibrinogen was conducted usinguncoated and plasma coated Dacron™ samples. The protein adsorption onthe coated samples was dramatically reduced (i.e., by a factor in excessof 20) when compared to adsorption on the uncoated Dacron™ control. Thedifferences were particularly acute in contrasting protein retained onthese surfaces after gently washing with 1% sodiumdodecyl sulfate (SDS)solution. The retained protein was barely detectable on the plasmatreated surfaces, being several orders of magnitude less than thatretained on the uncoated Dacron™ controls. This example indicates boththe durability and non-fouling properties of the coating composition ofthe invention.

[0136] Another sample was prepared in which the monomer of Example 1 wasplasma deposited onto a Dacron™ sample using an RF duty cycle of 10 msecon and 50 msec off and a peak power of 100 watts. The protein adsorptionon the coated samples was increased (i.e. by a factor of about 1.2) whencompared to adsorption on the uncoated Dacron™ control. This exampleshows that the non-fouling properties of coatings made at high RF dutycycle (⅕) are not as desirable as those coatings made at low RF dutycycle.

EXAMPLE 7

[0137] Samples were prepared as described in Example 1. These sampleswere then subjected to abrasive cleaning processes using standardcommercial contact lens cleansers following the lens cleaninginstructions provided by the manufacturers. Negligible changes insurface wetting were observed in comparing coated samples before andafter the abrasive cleaning processes as measured by the repeateddynamic water content angle method.

EXAMPLE 8

[0138] Samples were prepared as described in Example 1 and weredeposited on a silicone contact lens. These samples were subjected towater vapor autoclaving at 121° C. for 5 successive sterilizing cycles,each of 30 minutes duration. Negligible changes in the surfacewettabilities were observed in comparing samples before and afterautoclaving, indicating the durability of the coating compositions.

EXAMPLE 9

[0139] Silicone contact lens substrates were coated using a gradientlayering technique. In this process an initially high duty cycle plasmadeposition was carried out for 30 seconds at a power of 100 watts andplasma on/off cycle of 10 msec on and 20 msec off. Subsequently theplasma off time was increased sequentially to values of 50, 100, 150 and200 msec. At each on/off cycle, the plasma deposition was operated forseveral minutes with the final 10/200 deposition being carried out for 5minutes. The resulting gradient layered film structure exhibitedexceptional abrasion resistance and stability towards long term (i.e.,15 days) soaking under rapid (40 nm/min) flow conditions in PBS bufferat a pH of 7.2. XPS (X-ray Photoelectron Spectroscopy) analysis of thesurface composition of this layered structure revealed a high resolutionC(1s) spectrum having essentially the same composition as that observedfrom a direct 10 msec plasma on and 200 msec plasma off deposition at100 watts peak power.

EXAMPLE 10

[0140] The increased wettability of substrates having the coatingcomposition of this invention are shown by this example.

[0141] Water contact angle measurements were measured using both static(sessile drop) and dynamic (modified Wilhelmy plate) methods for coatedand uncoated substrates. Static measurements were made using distilledwater and a Rame'-Hart goniometer. Dynamic measurements were made usingsubstrates immersed in succession in three solutions, namely: saline;protein; and then again in saline. The protein solution contained amixture of albumen, Iysozyme and immunoglobin. Advancing and recedingcontact angles were measured under both static and dynamic conditions.In the static experiments, the advancing contact angles were measured at4 μL volume intervals as the water droplet was increased from 4 to 16μL. Receding angles were recorded as the droplet size was reduced from16 to 4 μL, again at 4 μL intervals. The dynamic measurements were eachrepeated four times as the sample was cycled up and down, with theaverage value being recorded for these four measurements.

[0142] Hydrophobic polymeric substrates (e.g. polyethylene; polyethyleneterephthalate) having static water contact angles in excess of 85° wereemployed. After plasma coating with coating compositions of thisinvention, the wettability of the surfaces increased, evidenced by thelarge decreases in the water contact angles. No substrate dependence wasobserved in achieving the improved wettabilities.

[0143] Table II provides results of static sessile drop water contactangles observed after treatment of an initially hydrophobic polymericsubstrate with plasma deposited films by plasma deposition ofdi(ethylene glycol) vinyl ether monomer. As show in Table II, allsamples revealed a decrease in water contact angles from the uncoatedsubstrate whose advancing angle was in excess of 85°. Also as shown inTable II, the exact extent of increased surface wettability is afunction of the plasma deposition conditions, with the wettabilitygenerally increasing as the average power employed during coating wasreduced. TABLE II STATIC CONTACT ANGLES RF Cycle Duty Times Peak AveragePlasma ON, OFF, Power Power Advancing Receding Coated msec msec (W) (W)Angle Angle Yes 10 200 100 4.76 60 33 Yes 10 200 50 2.38 46 30 Yes 10200 25 1.19 30 15 Yes 1 20 200 9.52 60 48 Yes 1 50 200 3.92 46 33 Yes 1100 200 1.98 33 22 Yes 1 200 200 0.995 32 23 No >85

[0144] The dynamic (i.e. modified Wilhelmy plate) contact anglemeasurements are listed in Table III for samples prepared by plasmadeposition of di(ethylene glycol) vinyl ether as described above, usingan RF on/off cycle of 10 msec on and 200 msec off and 100 watts peakpower. The advancing and receding contact angles are shown formeasurements in the three separate solutions, with these measurementsbeing carried out in succession. As in the static measurements, thedynamic studies reveal consistently lower contact angles for the coatedsubstrates with the surface wettability being appreciably higher forsamples immersed in the protein containing solutions.

[0145] Overall, the water contact angle measurements illustrate thetransformation of the initial hydrophobic polymer surface to ahydrophilic wettable surface as provided by the plasma depositedcoatings. TABLE III DYNAMIC CONTACT ANGLES Solution Advancing AngleReceding Angle Saline 61 43 Protein in Solution 25 22 Saline 45 43

EXAMPLE 11

[0146] Static (sessile drop) water contact angles, both advancing andreceding, were measured on polymeric substrates, plasma coated withdifferent monomers. The monomers employed were diethylene glycol vinylether (EO2V), diethylene glycol methyl vinyl ether (Methyl EO2V),diethylene glycol divinyl ether (Divinyl EO2V), and diethylene glycolethyl ether acrylate (Acrylate EO2V). These four coatings are given inthe table which follows All plasma films were deposited under theidentical RF on/off cycle of 10 msec on and 200 msec off and 100 wattspeak power. In each case, the uncoated hydrophobic polymeric surface(initially an advancing angle in excess of 85°) was transformed to ahighly wettable hydrophilic surface by the plasma deposition. As shownin Table IV, the hydrophilicity of the resulting surfaces wererelatively constant with each of these monomers, with the degree ofhysteresis between advancing and receding contact angles beingsignificantly reduced for the two monomers not terminated in —OH groups(i.e. Methyl EO2V and Divinyl EO2V).

[0147] The results obtained clearly illustrate the utility of employingthe coatings of this invention to transform the surface of the substratefrom hydrophobic to hydrophilic. TABLE IV STATIC CONTACT ANGLES MonomerAdvancing Angle Receding Angle EO2V 60 33 Methyl EO2V 53 47 Divinyl EO2V55 49 Acrylate EO2V 65 47

[0148] These examples show that the coating compositions of thisinvention can be used to provide non-fouling and hydrophilic surfaces tosubstrates, which have bulk properties which are well-suited forparticular applications. These coatings are particularly suited forbiomedical applications and in particular for contact or interoccularlenses.

[0149] The invention has been described in detail with particularreference to preferred embodiments thereof, but it will be understoodthat variations and modifications can be effected with the spirit andscope of the invention.

EXAMPLE 12

[0150] A sample on a silicon substrate was prepared from the monomer ofExample 1 using plasma deposition conditions of an RF on/off cycle of 10msec on and 200 msec off a peak power of 50 watts. XPS analysis of thisfilm revealed significantly more carbon atoms bonded to oxygen than toother carbon atoms. A sample prepared in this manner was then exposed toair for 10 months for a long term stability experiment. The sample wasthen re-analyzed by MPS. The relative concentration of C—O to C—C groupspresent on the surface had actually increased slightly revealingnegligible surface modification during air exposure, indicating thedurability of the coating composition. (FIGS. 4(a-b)).

EXAMPLE 13

[0151] Samples were prepared as described in Example 1 on quartzsubstrate. Analysis of these films by UV-VIS spectrometry showedcomplete light transmission over the entire visible region of theelectromagnetic spectrum, 380 to 800 nm.

EXAMPLE 14

[0152] Samples were prepared as described in Example 1 on Dacron™substrates at a fixed plasma-on to plasma-off ratio of 1 to 20 but withactual plasma-on and plasma-off pulse widths varying from 100 msec to 10μsec and 2000 msec to 200 μsec, respectively. All runs were carried outat a peak power of 50 watts and at constant flow rate and reactorpressure of the EO2V monomer. XPS high resolution C(1s) spectra showedthat a variation in the percent retention of the ether content of theplasma generated films was observed in these experiments with differentplasma-on and plasma-off pulse widths but all runs carried out at aconstant average power of 2.4 watts. (FIGS. 5(a-e)).

EXAMPLE 15

[0153] Samples are prepared as described in Example 1 using a 10 μsecplasma-on time and a 400 μsec plasma-off time. Again, highly wettablesurfaces can be obtained containing high C—O bonds relative to C—Cbonds, thus illustrating the production of usable films under ultrashort(i.e. microsecond) pulse times.

1. A device comprising a substrate and a coating composition, saidcoating composition being formed by the gas phase polymerization of agas comprising at least one organic compound, said gas phasepolymerization being pulsed, having a duty cycle of less than about ⅕,in which the pulse-on time is less than about 100 msec and the pulse-offtime is less than about 2000 msec, and said organic compound having thefollowing structure:

m=0-1; n=0-6, where Y represents C═O; R¹, R², R³, R⁴, R⁵, R⁶ and R⁷ eachindependently represents: HX OH, halogen, C₁-C₄ alkyl, C₁-C₄ alkene,C₁-C₄ diene, C₁-C₄alkyne, C₁-C₄ alkoxy, or C₁-C₄ alkyl halide; and R⁸represents: H, halogen, C₁-C₄ alkyl, C₁-C₄ alkene, C₁-C₄ diene, C₁-C₄alkyne, C₁-C₄ alkyl halide, C₁-C₄ aldehyde, C₁-C₄ ketone, C₁-C₄ epoxide,C₁-C₄ carboxylic acid, C₁-C₄ ester, —CH═CHR⁹, where R⁹ is H, halogen,C₁-C₄ alkyl, C₁-C₄ alkyl halide, C₁-C₄ aldehyde, C₁-C₄ ketone, C₁-C₄alkoxyl, C₁-C₄ epoxide, C₁-C₄ carboxylic acid, or C₁-C₄ ester, or —OR¹⁰,where R¹⁰ is H, halogen, C₁-C₄ alkyl, C₁-C₄ alkene, C₁-C₄ diene, C₁-C₄alkyne, C₁-C₄ alkyl halide, C₁-C₄ aldehyde, C₁-C₄ ketone, C₁-C₄ epoxide,C₁-C₄ carboxylic acid, or C₁-C₄ ester.
 2. The device of claim 1, whereinsaid organic compound is selected from the group of consisting of thefollowing structural formulas: R′C(R″)═C(R′″)—(OCH₂CH₂)_(n)—OR″″ andR′C(R″)═C(R″)—(OCH₂CH₂)—R″″ where R′, R″, R′″, and R″″ eachindependently represents H, a linear or branched alkyl having 1 to 5carbons; and n is 1 to
 5. 3. The device of claim 1, wherein said dutycycle is from about 1/10 to about 1/1000, and the pulse-on time is fromabout 1 μsec to about 100 msec, and the pulse-off time is from about 10μsec to about 2000 msec.
 4. The device of claim 1, wherein said organiccompound is di(ethylene glycol) vinyl ether, di(ethylene glycol) divinylether, or di(ethylene glycol) methyl vinyl ether.
 5. The device of claim1, wherein said substrate is a contact lens.
 6. The device of claim 1,wherein said gas phase polymerization is high voltage discharge, radiofrequency, microwave; ionizing radiation induced plasma polymerization;or photo induced polymerization; or a combination thereof.
 7. The deviceof claim 1, wherein said coating compositor is gradient layered bysystematically decreasing the duty cycle of said gas phasepolymerization.
 8. A device comprising a substrate and a coatingcomposition, said coating composition being formed by the gas phasepolymerization of a gas comprising at least one organic compound, saidgas phase polymerization being pulsed, having a variable duty cycle eachbeing of less than about ⅕, in which the pulse-on time is less thanabout 100 msec and the pulse-off time is less than about 2000 msec, andsaid organic compound having the following structure:

m=0-1; n=0-6, where Y represents C═O; R¹, R², R³, R⁵, R⁶ and R⁷ eachindependently represents: H, OH, halogen, C₁-C₄ alkyl, C₁-C₄ alkene,C₁-C₄ diene, C₁-C₄ alkyne, C₁-C₄ alkoxy, or C₁-C₄ alkyl halide; and R⁸represents: H, halogen, C₁-C₄ alkyl, C₁-C₄ alkene, C₁-C₄ diene, C₁-C₄alkyne, C₁-C₄ alkyl halide, C₁-C₄ aldehyde, C₁-C₄ ketone, C₁-C₄ epoxide,C₁-C₄ carboxylic acid, C₁-C₄ ester, —CH═CHR⁹, where R⁹ is H, halogen,C₁-C₄ alkyl, C₁-C₄ alkyl halide, C₁-C₄ aldehyde, C₁-C₄ ketone, C₁-C₄alkoxyl, C₁-C₄ epoxide, C₁-C₄ carboxylic acid, or C₁-C₄ ester, or —OR¹⁰,where R¹⁰ is H, halogen, C₁-C₄ alkyl, C₁-C₄ alkene, C₁-C₄ diene, C₁-C₄alkyne, C₁-C₄ alkyl halide, C₁-C₄ aldehyde, C₁-C₄ ketone, C₁-C₄ epoxide,C₁-C₄ carboxylic acid, or C₁-C₄ ester.
 9. The device of claim 8, whereinsaid organic compound is selected from the group of consisting of thefollowing structural formulas: R′C(R″)═C(R′″)—(OCH₂CH₂)_(n)—OR″″ andR′C(R″)═C(R′″)—(OCH₂CH₂)_(n)—R″″ where R′, R″, R′″, and R″″ eachindependently represents H, a linear or branched alkyl having 1 to 5carbons; and n is 1 to
 5. 10. The device of claim 8, wherein said dutycycles vary from about 1/10 to about 1/1000, and the pulse-on timevaries from about 1 μsec to about 100 msec, and the pulse-off timevaries from about 10 μsec to about 2000 msec.
 11. The device of claim 8,wherein said organic compound is di(ethylene glycol) vinyl ether,di(ethylene glycol) divinyl ether, or di(ethylene glycol) methyl vinylether.
 12. The device of claim 8, wherein said substrate is a contactlens.
 13. The device of claim 8, wherein said gas phase polymerizationis high voltage discharge, radio frequency, microwave; ionizingradiation induced plasma polymerization; or photo inducedpolymerization; or a combination thereof.
 14. The device of claim 8,wherein said coating composition is gradient layered by systematicallydecreasing the duty cycle of said gas phase polymerization.
 15. A methodfor plasma depositing a coating to a solid substrate, said methodcomprising: subjecting an organic compound having carbon, hydrogen andoxygen elements and a vinyl moiety to a gas phase polymerizationutilizing a pulsed discharge having a duty cycle of less than about ⅕,in which the pulse-on time is less than about 100 msec and the pulse-offtime is less than about 2000 msec.
 16. The method of claim 15, whereinsaid duty cycle is from about 1/10 to about 1/1000, and the pulse-ontime is from about 1 μsec to about 100 msec, and the pulse-off time isfrom about 10 μsec to about 2000 msec.
 17. The method of claim 15,wherein said organic organic compound is di(ethylene glycol) vinylether, di(ethylene glycol) divinyl ether, or di(ethylene glycol) methylvinyl ether.
 18. The method of claim 15, wherein said substrate is acontact lens.
 19. The method of claim 15, wherein said gas phasepolymerization is high voltage, radio frequency, microwave; ionizingradiation induced plasma polymerization; or photo inducedpolymerization; or a combination thereof.
 20. The method of claim 15,wherein said pulsed discharge comprises a series of variable duty cycle.21. The method of claim 15, wherein said organic compound further havinga halogen element.
 22. The device prepared by the method of claim 15.